Exposure to cyclic intermittent hypoxia increases expression of functional NMDA receptors in the rat carotid body.
Although large quantities of glutamate are found in the carotid body, to date this excitatory neurotransmitter has not been assigned a role in chemoreception. To examine the possibility that glutamate and its N-methyl-d-aspartate (NMDA) receptors play a role in acclimatization after exposure to cyclic intermittent hypoxia (CIH), we exposed male Sprague-Dawley rats to cyclic hypoxia or to room air sham (Sham) for 8 h/day for 3 wk. Using RT-PCR, Western blot analysis, and immunohistochemistry, we found that ionotropic NMDA receptors, including NMDAR1, NMDAR2A, NMDAR2A/2B, are strongly expressed in the carotid body and colocalize with tyrosine hydroxylase in glomus cells. CIH exposure enhanced the expression of NMDAR1 and NMDAR2A/2B but did not substantially change the level of NMDAR2A. We assessed in vivo carotid sinus nerve activity (CSNA) at baseline, in response to acute hypoxia, in response to infused NMDA, and in response to infused endothelin-1 (ET-1) with and without MK-801, an NMDA receptor blocker. Infusion of NMDA augmented CSNA in CIH rats (124.61 +/- 2.64% of baseline) but not in sham-exposed rats. Administration of MK-801 did not alter baseline activity or response to acute hypoxia, in either CIH or sham animals but did reduce the effect of ET-1 infusion on CSNA (CSNA after ET-1 = 160.96 +/- 8.05% of baseline; ET-1 after MK-801 = 118.56 +/- 9.12%). We conclude that 3-wk CIH exposure increases expression of NMDA functional receptors in rats, suggesting glutamate and its receptors may play a role in hypoxic acclimatization to CIH.
Liu
Yuzhen
Y
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Ji
En-Sheng
ES
Xiang
Shuanglin
S
Tamisier
Renaud
R
Tong
Jingli
J
Huang
Jianhua
J
Weiss
J Woodrow
JW
D000222:Adaptation, Physiological; D000818:Animals; D015153:Blotting, Western; D002344:Carotid Body / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002346:Carotid Sinus / Q000294:innervation; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D019332:Endothelin-1 / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D016202:N-Methylaspartate / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015854:Up-Regulation
D000076122:Disks Large Homolog 4 Protein; D019332:Endothelin-1; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016202:N-Methylaspartate; D016194:Receptors, N-Methyl-D-Aspartate; D014446:Tyrosine 3-Monooxygenase; C501449:Dlg4 protein, rat; C121001:NR2B NMDA receptor